Role of the endocannabinoid system in human pain sensitivity, pain plasticity, pain habituation, and neurogenic and non-neurogenic inflammation.

This subproject dealt with the role of endocannabinoids in pain perception and implicit pain memory in human subjects. The core project of SP5 is the analysis of genotype phenotype correlations, for which we have developed methods for pain plasticity and sensitivity during the first funding period. Phenotyping included HFS-induced hyperalgesia and LFS-induced reversal of pain LTP as well as a standardized battery of quantitative sensory testing (QST) and a pain-screening test in 90, 133 and 390 subjects, respectively. We analyzed 22 SNPs in ECS candidate genes for genotyping. In a preliminary analysis we revealed a significant impact of five SNPs on pain plasticity. Four of these polymorphisms map to the CNR1 gene coding for the CB1 receptor and one maps to the gene coding for DAGLβ.

The focus of SP5 during the second funding term will be the analysis of genes encoding for members of the human ECS (CNR1, CNR2, DAGLα, DAGLβ and FAAH) on individual variability of pain sensitivity, pain plasticity, pain habituation, and development of clinical persistent pain. Pharmacologically, we will investigate the peripheral and/or central antinociceptive action of the endocannabinoid-related lipid PEA in neurogenic and non-neurogenic human models of inflammation. Using positron emission tomography (PET), changes in CB1 receptor availability in the brain will be examined during human nociceptive processing and pain LTP.